Electrophoresis apparatuses that utilize capillary tubes for rapid processing of mass data are widely used in DNA nucleotide sequence analyses. The capillary tubes used are generally glass tubes having an inner diameter of 1 to 800 μm, an outer diameter of 50 to 1,000 μm and a length of 50 to 2,000 mm, which is coated with a polymer to a thickness of 10 to 30 μm, among which a capillary tube of an appropriate size is employed. Polymer, generally polyimide, is coated to enhance the mechanical strength and give flexibility to the fragile glass tube for easy handling. However, since a sample migrating inside a capillary tube is detected by irradiating the fluorescence-labeled sample with a laser beam from outside the capillary tube and detecting the excited fluorescence, a polymer coating with a poor light transmittance will interfere with the sample detection. Thus, it is necessary to selectively remove the polymer coating for a length of about 1 to 20 mm around the periphery of the capillary tube. The portion removed of the polymer coating for an increased light transmittance is generally called a “window”.
In order to process a window for a capillary tube, a technique in which a polymer coating is removed by burning with a lighter flame is generally employed when the number of capillary tubes is small. When the number of the capillary tubes is large, a technique such as one disclosed in JP-A-5-232085 may be employed in which a plurality of capillary tubes are supported at the same time to burn and remove predetermined regions of the polymer coating with a gas burner. However, burning with a lighter or a gas burner will leave cinders on the surfaces of the capillary tubes, and thus requires an after-treatment for wiping the cinders away with a wiper such as paper or cloth, which causes an increase in the production cost. Furthermore, wiping with the wiper may damage the exposed glass tube region. If the exposed glass tube region has a damage, the capillary tube can be susceptible to breakage during operations such as mounting the capillary tube on an apparatus. In addition, controlling the temperature of the flame is difficult since burning at a low temperature will leave a large amount of cinders and burning at a high temperature will result in deformation or poor transmittance of the glass capillary tube. Cinders on the window will interfere with the detection of fluorescence excited by laser irradiation.
In order to process a window by burning the polymer coating under a controlled temperature, techniques using an electric heater as disclosed in U.S. Pat. No. 4,940,883 (1990), JP-A-10-206383, JP-A-11-230939 may be employed. However, even under a controlled temperature, polymer coating is difficult to be burnt completely at or below an allowable continuous temperature of synthesized quartz (about 950° C.) that is generally used for making the glass tube, and a border between regions heated and unheated by the electric heater always includes insufficiently heated parts. As a result, after-treatment for wiping away the cinders is inevitable. Even if the window is elegantly processed, remaining cinders may fall off after the capillary tube is mounted on the electrophoresis apparatus, and may stick to a part that may cause an adverse effect on detection.
As a processing technique other than burning, JP-A-6-74938 discloses a technique for mechanically removing the coating with a scraper. However, it is difficult to remove the coating efficiently without damaging the glass tube. According to another technique, the polymer coating will be sublimed through ablation with an excimer laser. However, this technique requires an expensive device and a large installation area. Reagents such as hot sulfuric acid and hydrazine may be used for removing the coating. However, they are hazardous and thus have drawbacks such as difficult handling, requirement of after-treatment, requirement of waste fluid processing and a risk of causing adverse effect on the environment. Above all, since they are liquid, it is difficult to provide a mask for exposing only a region to be processed into the window to immerse the tube in the drug.
A capillary tube provided with a window is susceptible to breakage because stresses caused upon bending or pulling the capillary tube may concentrate on the damage of the exposed glass region. The polymer coating is provided basically to enhance the mechanical strength and flexibility of the glass tube. Another reason for easy breakage of the capillary tube by the concentration of the stresses on the exposed portion is the profile of the edge of the coating at the window. When the edge of the coating at the window is removed generally perpendicular to the longitudinal direction of the capillary tube, the stresses will be concentrated on the edge of the coating at the window upon bending the tube and cause easy breakage.
In a multi-capillary electrophoresis apparatus, a plurality of capillary tubes are used as a multi-capillary array with the windows arranged in parallel to form a plane with the ends of the tubes being aligned. The windows of the multi-capillary array are supported by a holder so that the tubes are held secure. Capillary tubes having windows are used to produce the multi-capillary array. Since the mechanical strength of the glass capillary tubes with exposed windows is poor, they are difficult to be handled upon assembly, which interferes with automation of producing a multi-capillary array.
The above-described conventional techniques have adverse effects on the strength and the measurement due to damage, deformation, poor transmittance or the like of a glass capillary tubes and have the following problems: requirement of an after-treatment following the coating removal; requirement of an expensive device and a large installation area for the device; or use of a reagent that may be hazardous to human and the environment. In addition, conventional techniques have a problem of being susceptible to breakage which is caused by concentration of stresses on the edge of the coating at the window of the capillary tube, and a problem of automation in assembling fragile capillary tubes having windows being impossible for producing a multi-capillary array.
The present invention has an objective of providing a tough capillary tube provided with a window, which is produced in a safe and inexpensive manner by a method that causes no adverse effect, such as damage, deformation, poor transmittance or the like on a glass tube as a main body of the capillary tube, which may interfere with optical detection of a sample by an electrophoresis apparatus and while saving trouble such as wiping after the coating removal. The present invention also has an objective of providing means for automating production of a multi-capillary array, which has been impossible.